DESCRIPTION (Investigator's Abstract): This is a phase I application in which the goal is to develop a therapeutic agent which would replace heparin. Although heparin is the best drug for treatment of thromboembolic disease, it is unstable if administered orally and much therefore be used by the intravenous or subcutaneous route. In addition, the thrombocytopenia and both bleeding and thrombosis, which can emerge as complications of this therapy, remain a clinical problem. Recently, in a preliminary report, a group of sulfonated bislactobionic acid amines have been demonstrated to possess anticoagulant and antiocclusive properties comparable to those currently attainable with commercial heparin. Starting with compounds such as maltose and cellobiose, the disaccharide is oxidized and condensed with short chain diamines and then sulphonated. The applicant's company produces large quantities of lactobionic for stabilization of erythromycin and organs for transplant. During a literature search, the applicant found that sulphonated bis-lactobionic acid amines are potential anticoagulants. In heparin, the 3-0'-sulphate on the middle sugar is essential for anticoagulant activity. The applicants will produce carbohydrates of various structure which may have an improved heparin-like activity. The compounds will be initially tested for anticoagulant properties in phase I and, later in phase II, their antithrombotic activity will be evaluated. The advantage of using maltose as a beginning disaccharide is that it may not be digested to the same degree as other sugars. Cellobiose is another starting disaccharide which may not be cleaved by mammalian digestive enzymes. Also, the compounds are rather small, soluble and may be readily absorbed. These small polymers are also non-toxic. Anticoagulant properties of the final compounds generated will be examined for their ability to prolong the activated partial thromboplastin time and the thrombin time. The standard will be heparin, 175 units/mg. Dr. Tollefsen, one of the consultants, will examine the effects of active compounds on the rate of thrombin inhibition by purified antithrombin III and heparin cofactor II as established in his laboratory.